We are studying the phosphorylation of proteins in the nucleus of eucaryotic cells as catalyzed by protein kinases found in the acidic protein fraction. Our interest is primarily the acid labile protein phosphates formed. Thus far two kinases have been discovered one with a pH optimum of 6.5; the other with a pH optimum of 9.0. The pH 6.5 kinase apparently forms lysine phosphate in histone I while the pH 9.0 kinase forms histidine phosphate in histone IV. We are studying the role of these enzymes in replicative and transcriptional events. We also are studying the formation and release of mucopolysaccharides by normal and malignant cells in culture. This process is apparently under fine control by cyclic AMP and may be related to contact inhibition - or the lack of it. Up to now our efforts have mainly been involved with the analytical procedures for mucopolysaccharides.